Methods of using magnetic fields to uniformly induce electric fields for therapeutic purposes

ABSTRACT

The present invention provides a method and apparatus for delivering an electric field to a body by delivering a first magnetic field from a first coil in a first orientation to a body and directed at a desired target within the body, and delivering a second magnetic field from a second coil in a second orientation directed at the desired target within the body to induce an electric field across the desired target, wherein only one magnetic field is delivered to the body at any one time.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of application Ser. No. 11/055,984,filed Feb. 14, 2005, now U.S. Pat. No. 7,587,230, which is acontinuation-in-part of application Ser. No. 10/426,720, filed May 1,2003, now U.S. Pat. No. 6,856,839, which is a divisional of applicationSer. No. 09/737,546, filed Dec. 18, 2000 now U.S. Pat. No. 6,853,864,which claims priority from U.S. Provisional Application No. 60/179,738,filed Feb. 2, 2000. The entire contents and disclosures of the aboveapplications are incorporated herein by reference.

BACKGROUND

1. Field of the Invention

The present invention relates generally to the use of magnetic fields,and more particularly, to methods of using magnetic fields to uniformlyinduce electric fields for therapeutic purposes.

2. Related Art

Exposure to electromagnetic fields (EMFs) has become an increasinglyuseful tool in the treatment of many medical conditions. For example,exposure to time-varying magnetic fields is an accepted method ofaccelerating bone and wound healing. For example, EMFs may be used tolimit damage to a heart during a heart attack and to protect bone marrowduring chemotherapy and x-ray therapy for destruction of tumors.

When an EMF is applied to a cell, the electric field acting on the cellis the main mechanism by which the EMF affects the cell. For mostpurposes, the use of a low frequency time-varying magnetic field is themost convenient and controllable method of causing an electric field toappear across the tissue to be treated. A time-varying magnetic fieldmay be created external to the body (for example with a pair of coilsand a time-varying current source). When this field enters a body, itinduces (by Faraday's Law) a time-varying electric field. It is fairlystraightforward to create a uniform magnetic field in a body because thebody's magnetic properties are quite uniform. However, the inducedelectric field is very non-uniform because the body's electricalconductivity may vary enormously from organ to organ (e.g., lung toheart) and within an organ (e.g., heart muscle to heart blood).

This lack of uniformity represents a serious limitation in thetherapeutic application of time-varying magnetic fields. A good exampleof this limitation is in the use of magnetic fields to limit damage tothe heart after an ischemic event (e.g., heart attack). Application ofthe magnetic field for a period of 30 minutes or more induces activationof heat shock proteins (hsps) in the cells of the heart muscle. Thesehsps act to protect the heart from cell death (necrosis) during theperiod in which the stoppage of blood flow (ischemia) causes cellstress. The problem that exists with this technique is that the inducedelectric fields vary so greatly that in many regions of the heart theinduced electric field is not great enough to cause the cells to producehsps. For example, the lung is a high resistance region adjacent to theheart. As a result, if the induced electric field passes through boththe lung and heart, most of the field will appear across the lung andvery little in the heart. Even if the induced electric field is appliedin a direction that does not cross the lung, there will be regions inthe heart that do not experience a significant electric field becausethe blood has such a low conductivity relative to the heart muscle.

Which regions of an organ do not experience a significant electric fielddepends critically upon the direction of the applied magnetic field, andthus the direction of the induced EMF. One proposed solution may be tosimply apply fields in the x, y and z directions simultaneously. Thishowever does not work since the vector sum of these fields would besimply a new magnetic field in a single direction.

SUMMARY

According to a first broad aspect of the present invention, there isprovided a method of delivering an electric field to a body, comprisingdelivering a polarized magnetic field in a first direction to a body anddirected at a desired target within the body; and changing the deliverydirection of the magnetic field to a second direction directed at thedesired target to induce an electric field across the desired target.

According to a second broad aspect of the present invention, there isprovided a method of delivering an electric field to a body, comprisingdelivering a first magnetic field from a first coil in a firstorientation to a body and directed at a desired target within the body;and delivering a second magnetic field from a second coil in a secondorientation directed at the desired target within the body to induce anelectric field across the desired target, wherein only one magneticfield is delivered to the body at any one time.

According to a third broad aspect of the present invention, there isprovided a method of delivering an electric field to a body, comprisingdelivering a first magnetic field from a first coil in a firstorientation to a body and directed at a desired target within the body;delivering a second magnetic field from a second coil in a secondorientation directed at the desired target within the body; anddelivering a third magnetic field from a third coil in a thirdorientation directed at the desired target within the body to induce anelectric field across the desired target.

According to a fourth broad aspect of the present invention, there isprovided an apparatus for delivering an electric field to a body,comprising a means for delivering a first magnetic field from a firstcoil in a first orientation to a body and directed at a desired targetwithin the body; a means for delivering a second magnetic field from asecond coil in a second orientation directed at the desired targetwithin the body to induce an electric field across the desired target;and a means for alternating a current between the first coil and thesecond coil.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will be described in conjunction with the accompanyingdrawings, in which:

FIG. 1 is a schematic representation of a coil arrangement in accordancewith an embodiment of the present invention in which 2 pairs of coilsare oriented perpendicular to each other;

FIG. 2 is a schematic representation of a coil arrangement in accordancewith an embodiment of the present invention in which 2 pairs of coilsare oriented perpendicular to each other;

FIG. 3 is a schematic representation of a coil arrangement in accordancewith an embodiment of the present invention using 3 pairs of coils; and

FIG. 4 is a graph of on/off intervals and percentage of maximum responsefor different models of EMF-induced effects, including hypoxiaprotection (circles) and changes in enzyme activity (squares).

DETAILED DESCRIPTION

It is advantageous to define several terms before describing theinvention. It should be appreciated that the following definitions areused throughout this application.

DEFINITIONS

Where the definition of terms departs from the commonly used meaning ofthe term, applicant intends to utilize the definitions provided below,unless specifically indicated.

For the purposes of the present invention, the term “linearly polarizedmagnetic field” refers to a magnetic field that varies in time but whosedirection is always directed along a given fixed line.

For the purposes of the present invention, the term “circularlypolarized magnetic field” refers to a magnetic field whose field vectorrotates about a fixed axis and appears to go around in a circle.

For the purposes of the present invention, the term “linear verticalfield” refers to a linearly polarized field whose field vector isoriented in the vertical direction.

For the purposes of the present invention, the term “linear horizontalfield” refers to a linearly polarized field whose field vector isoriented in the horizontal direction.

For the purposes of the present invention, the term “circular verticalfield” refers to a circularly polarized field in which the field vectorrotates about the vertical axis.

For the purposes of the present invention, the term “circular horizontalfield” refers to a circularly polarized field in which the field vectorrotates about the horizontal axis.

For the purposes of the present invention, the term “uniform electricfield” refers to an induced electric field which is essentially constantin all of the tissues to be treated.

For the purposes of the present invention, the term “orientation” refersto the arrangement, configuration, direction, etc. of the elementidentified, such as the orientation of the magnetic field.

DESCRIPTION

The present invention provides a method and apparatus for delivering anelectric field to a body by delivering a first magnetic field from afirst coil in a first orientation to a body and directed at a desiredtarget within the body, and delivering a second magnetic field from asecond coil in a second orientation directed at the desired targetwithin the body to induce an electric field across the desired target,wherein only one magnetic field is delivered to the body at any onetime. The present invention provides an increase in the uniformity ofthe induced electric field. Increased uniformity is beneficial because,if the induced electric field is not uniform, its value may (in someregions of the tissue to be treated) fall below the threshold valuenecessary to induce beneficial biological effects, and thus thetreatment may be only partially effective.

Under certain conditions, the effectiveness of a magnetic fieldtreatment (whose duration may be, for example, from approximately 30 toapproximately 60 minutes duration) may be significantly enhanced if thedirection of the magnetic field direction is changed in time during thetreatment.

A linearly polarized magnetic field may be used that alternatelyswitches back and forth from one direction (e.g., vertical) to aperpendicular direction (e.g., horizontal). In other embodiments of thepresent invention, the direction of the field may be switchedapproximately 90 degrees +/−30 degrees with respect to the originaldirection of the field.

According to embodiments of the present invention, the timing of theexposure is an important element of an effective treatment. According toan embodiment of the present invention, the magnetic field remains inany given direction for at least 5 seconds before switching to a newdirection. In some embodiments, the minimum time of exposure in anydirection is greater than 10 seconds before switching. In someembodiments of the present invention, the maximum time of exposure inany direction is 300 seconds or more before switching. Thus, a suitableduration for exposure in any one direction may be from approximately 5seconds to approximately 300 seconds or more, preferably fromapproximately 10 to approximately 30 seconds. The timeframes forexposure may be modified depending on the tissues or cells beingtreated, the frequency of exposure, and depending on the length of timebetween treatments.

A magnetic field for use in the present invention may be generated with,for example, 2 pairs of coils that are oriented perpendicular to eachother and in which an AC current alternately flows in one pair and thenin the perpendicular pair. Such an arrangement provides a field in twoperpendicular directions. FIGS. 1 and 2 provide schematicrepresentations of coil arrangements in accordance with embodiments ofthe present invention in which 2 pairs of coils are orientedperpendicular to each other.

One goal of the present invention is to obtain a uniform inducedelectric field. Thus, according to an embodiment of the presentinvention, it is preferable to start with a reasonably uniform magneticfield. Current flowing in a single coil may be used in the presentinvention, although such an arrangement creates a relatively non-uniformmagnetic field, thus introducing some of the problems mentioned above. Apair of coils which lie in planes that are perpendicular to each otheryields much more uniform magnetic fields when current flows in them insuch a way that the fields of the two coils are additive in the regionbetween the coils.

In another arrangement of the present invention, two pairs of coils arearranged perpendicular to each other and the AC current in one pair is90 degrees out of phase with the other pair of coils so that a circularpolarized magnetic field is created. According to embodiments of thepresent invention, the currents may be other than 90 degrees out ofphase, such as 90 degrees +/−30 degrees. If the currents are out ofphase, but not 90 degrees out of phase, then the resultant field may beconsidered to be composed of a circular polarized field (caused by thatcomponent of the currents which are 90 degrees out of phase) and alinearly polarized magnetic field (caused by the component of thecurrents which are in phase with each other). This is generally lesseffective than the 90 degree out of phase condition, however, such anarrangement is encompassed within the scope of the present invention.Thus, for example, a magnetic field is created which rotates from, forexample, the vertical direction to the horizontal directioncontinuously. Such an arrangement provides a field in two perpendiculardirections.

Another embodiment of the present invention provides for a circularpolarized magnetic field in which the circular field has a plane with adirection that is switched in time to a perpendicular direction. Thismay be accomplished with 3 pairs of coils oriented perpendicular to eachother. Such an arrangement may be seen in FIG. 3. These coils may bedesignated coil pair 302, coil pair 304 and coil pair 306, respectively.In an exemplary embodiment of the present invention, AC current flowsfirst in coil pairs 302 and 304. The currents in these coils may be 90degrees out of phase. After a period of time, which is, for example, atleast approximately 5 seconds, preferably greater than approximately 10seconds, but typically not greater than approximately 300 seconds, thecurrent is switched so that coil pair 302 and coil pair 306 areenergized with or without 90 degree out of phase currents. In anembodiment of the present invention, coil pair 304 and coil pair 306 arealso 90 degrees out of phase. Such an arrangement provides a field inthree perpendicular directions.

According to embodiments of the present invention, the frequency of theapplied magnetic field is at least approximately 20 Hz. In otherembodiments of the present invention, the frequency of the appliedmagnetic field may be approximately 20 Hz to approximately 60 Hz, orgreater. The current in the coils should be great enough to create amagnetic field in the tissue being treated which is sufficient to inducean electric field at 60 Hz which is greater than about 10microvolts/meter. At frequencies above 60 Hz, the magnetic field mayremain the same as that calculated above for the 60 Hz condition. Atfrequencies below 60 Hz, the magnetic field should increase inverselywith the decrease in frequency. Thus, for example, at 20 Hz the magneticfield should be 3 times that needed at 60 Hz.

For use in the present invention, any suitable magnetic field generatingcoils may be used, including, Helmholtz coils, etc. FIGS. 1, 2 and 3show schematic representations of coil arrangements, and should not beconstrued to limit the application of the present invention to sucharrangements. Coils of the present invention may be of various shapesand arrangements now known or later developed.

The present invention may be used in various treatment protocolsincluding single treatments or multiple treatments on one day, in oneweek, or over several weeks or months, depending on the particularapplication. A single treatment may be provided for a period of seconds,minutes or hours depending on the particular application.

The present invention improves the effectiveness of magnetic fieldtherapy when treating various organs in the body for conditions rangingfrom cancer to heart attacks. In addition, when time varying magneticfields are used as a prophylactic to protect against adverse stresses,the present invention makes the process more effective. Thus, thepresent invention may be used in combination with known or laterdeveloped methods, such as those described in U.S. patent applicationSer. Nos. 09/737,546 and 10/426,720, which relate the use of EMFs andtemporal constancy requirements to the ability to focus the biologicaleffect of an EMF, the entire contents and disclosures of which arehereby incorporated by reference.

The following data show the impact of the present invention. Studieswere conducted to investigate the ability of induced electric fields ina rat heart to protect against a simulated heart attack. In this study,magnetic fields were applied in only one of 2 directions (vertical orhorizontal linear, relative to the rat). As may be seen in the datapresented in Table 1 below, no statistically significant reduction innecrotic heart tissue was observed. This was because large regions ofthe heart muscle were not being exposed to an electric field capable ofinducing a biological effect (in this case, ischemic protection).

TABLE 1 Effect of EMFs on Damage after Heart Attack Damage (InfarctSize)* EMF Exposure Polarization # Pairs Control EMF Exposure VerticalLinear 4 63.9 ± 3.2 60.8 ± 2.7 Horizontal Linear 4 57.3 ± 2.2 53.7 ± 1.9*Data expressed as mean ± SEM

In further studies, however, it was discovered that by changing in timethe direction of the applied magnetic field, such that more than oneplane of magnetic field application was used during the exposure, athree-fold improvement in salvage of the myocardial tissue could beobtained. In this second study, rats were exposed either to a circularlypolarized field (in the vertical or horizontal plane), or a field inwhich the direction of the applied magnetic field switched from verticalto horizontal every 30 seconds. In these experiments, a reduction of˜15% in necrotic tissue was observed compared to the reduction of ˜5% inTable 1.

TABLE 2 Effect of EMFs on Damage after Heart Attack Damage (InfarctSize)* EMF Exposure Polarization # Pairs Control EMF Exposure VerticalCircular 6 54.0 ± 3.6 46.5 ± 2.2^(⊥) Horizontal Circular 6 51.4 ± 5.143.9 ± 4.6^(⊥) 30 Sec-Alternating Between 8 59.5 ± 1.3 52.4 ± 2.1^(⊥)Vertical Linear, and Horizontal Linear *Data expressed as Mean ± SEM^(⊥)P < 0.05 vs. control by paired T-Test (very significant)

As is summarized in Tables 1 and 2 above, all of the linear,one-directional EMFs (vertical or horizontal) were only marginallyeffective in reducing the infarct size following simulated heart attack.This is to be expected given the non-uniform nature of the electricfields induced by these one-directional exposures. However, the otherEMF exposures tested (vertical circular, horizontal circular oralternating) resulted in significant improvements in reduction of heartdamage. These findings support the notion that multi-direction EMFexposures are capable of inducing more uniform electric fields, andthus, significant biological effects in the tissue.

According to an embodiment of the present invention, amulti-directional, magnetic field exposure approach may be coupled withspecific timing protocols in order to increase its effectiveness.Specific time scales for exposure induce a more robust biologicaleffect. It has previously been described that if a magnetic fieldexposure is temporally constant for some minimal period of time, forexample, greater than approximately 10 seconds, a full biological effectmay be achieved. FIG. 4 shows this phenomenon for a number of differentmodels of EMF-induced effects, including hypoxia protection (circles)and changes in enzyme activity (squares). As may be seen in FIG. 4,according to an embodiment of the present invention, a minimum on/offtime interval of approximately 10 seconds achieves a maximum inducedbiological effect. Thus, in an embodiment of the present invention, thedirection of the field is not switched on time scales less than about 10seconds. In other embodiments, however, the time scales may be more orless than 10 seconds between switching field direction.

Furthermore, whereas all uniaxial exposures create inhomogeneous inducedelectric fields in the tissue, most multi-axial exposures do this aswell. This is because, when tissues are exposed to multi-directionalfields simultaneously, the actual applied field is a sum of all thedifferent-direction applied fields, resulting in a one-directionalmagnetic field exposure vector. In order to avoid this scenario, themulti-directional exposures may be applied other than simultaneously.One way to achieve this is through the use of a circularly-polarizedmagnetic field, whose direction continually changes (e.g., vertical orhorizontal circular shown in Table 2 above). However, this method yieldsinduced electric fields that are more difficult to quantify and is notalways the most effective means of inducing electric fields in tissue,since there may still be regions with sub-threshold induced electricfields. Instead, according to an embodiment of the present invention,the use of applied magnetic fields (linear or circular), whosedirection/orientation changes at certain time intervals to a secondplane of exposure (as evidenced by the alternating linear data given inTable 2) is provided. If a magnetic field exposure is temporallyconstant for some minimal period of time (for example, greater thanapproximately 10 seconds), a full biological effect may be achieved.

All documents, patents, journal articles and other materials cited inthe present application are hereby incorporated by reference.

Although the present invention has been fully described in conjunctionwith several embodiments thereof with reference to the accompanyingdrawings, it is to be understood that various changes and modificationsmay be apparent to those skilled in the art. Such changes andmodifications are to be understood as included within the scope of thepresent invention as defined by the appended claims, unless they departtherefrom.

1. A method of delivering an electric field to a body, comprising:delivering a first magnetic field from a first coil in a firstorientation to a body and directed at a desired target within the body;and delivering a second magnetic field from a second coil in a secondorientation directed at said desired target within the body to induce anelectric field across said desired target, wherein only one magneticfield is delivered to the body at any one time.
 2. The method of claim1, wherein at least one of said first magnetic field in a firstorientation and said second magnetic field in a second orientationcomprises a linearly polarized magnetic field.
 3. The method of claim 1,wherein at least one of said first magnetic field in a first orientationand said second magnetic field in a second orientation comprises acircularly polarized magnetic field.
 4. The method of claim 1, whereinat least one of said first coil and said second coil comprises a coilpair.
 5. The method of claim 1, wherein said first orientation isperpendicular to said second orientation.
 6. The method of claim 1,further comprising delivering a third magnetic field from a third coilin a third orientation.
 7. The method of claim 6, wherein said firstorientation, said second orientation and said third orientation are eachperpendicular to the orientations of the other coils.
 8. The method ofclaim 1, wherein said first magnetic field is delivered in said firstorientation for at least 5 seconds before the delivery orientation ischanged to said second orientation of said second magnetic field.
 9. Themethod of claim 1, wherein said first magnetic field is delivered insaid first orientation for at least 10 seconds before the deliveryorientation is changed to said second orientation of said secondmagnetic field.
 10. The method of claim 1, wherein said first magneticfield is delivered in said first orientation for at least 30 secondsbefore the delivery orientation is changed to said second orientation ofsaid second magnetic field.
 11. The method of claim 1, wherein saidfirst magnetic field is delivered in said first orientation for no morethan 300 seconds before the delivery orientation is changed to saidsecond orientation of said second magnetic field.
 12. The method ofclaim 1, wherein the magnetic fields are delivered to the body for atotal of approximately 30 minutes to approximately 60 minutes.
 13. Themethod of claim 1, wherein the target comprises cancer cells.
 14. Themethod of claim 1, wherein the target comprises heart tissue.
 15. Themethod of claim 1, wherein an AC current flows alternately through saidfirst coil and said second coil.
 16. The method of claim 15, wherein theAC current flowing through said first coil is approximately 90 degreesout of phase with the AC current flowing through said second coil. 17.The method of claim 15, wherein the AC current flowing through saidfirst coil is from approximately 60 degrees to approximately 120 degreesout of phase with the AC current flowing through said second coil.